47 research outputs found

    Implementing precision methods in personalizing psychological therapies: barriers and possible ways forward

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    This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: No data was used for the research described in the article.Highlights: • Personalizing psychological treatments means to customize treatment for individuals to enhance outcomes. • The application of precision methods to clinical psychology has led to data-driven psychological therapies. • Applying data-informed psychological therapies involves clinical, technical, statistical, and contextual aspects

    S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas

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    Despite marked success in treatment with immune checkpoint inhibitor (CPI), only a third of patients are responsive. Thus, melanoma still has one of the highest prevalence and mortality rates; which has led to a search for novel combination therapies that might complement CPI. Aberrant methylomes are one of the mechanisms of resistance to CPI therapy. S-adenosylmethionine (SAM), methyl donor of important epigenetic processes, has significant anti-cancer effects in several malignancies; however, SAM's effect has never been extensively investigated in melanoma. We demonstrate that SAM modulates phenotype switching of melanoma cells and directs the cells towards differentiation indicated by increased melanogenesis (melanin and melanosome synthesis), melanocyte-like morphology, elevated Mitf and Mitf activators’ expression, increased antigen expression, reduced proliferation, and reduced stemness genes' expression. Consistently, providing SAM orally, reduced tumor growth and progression, and metastasis of syngeneic BRAF mutant and wild-type (WT) melanoma mouse models. Of note, SAM and anti-PD-1 antibody combination treatment had enhanced anti-cancer efficacy compared to monotherapies, showed significant reduction in tumor growth and progression, and increased survival. Furthermore, SAM and anti-PD-1 antibody combination triggered significantly higher immune cell infiltration, higher CD8+ T cells infiltration and effector functions, and polyfunctionality of CD8+ T cells in YUMMER1.7 tumors. Therefore, SAM combined with CPI provides a novel therapeutic strategy against BRAF mutant and WT melanomas and provides potential to be translated into clinic

    Supplementary Material for: Altered T Helper 17 Responses in Children with Food Allergy

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    <b><i>Background:</i></b> While a central role for the T helper (Th) 1/Th2 axis in food allergy has been established, the Th17 response in food-allergic humans has not been addressed. <b><i>Methods:</i></b> Th17 responses in 18 peanut-allergic children, who were also allergic to at least one additional food allergen, were assessed relative to 15 age-matched healthy controls. To account for the atopy background in the allergic children, 7 atopic, but not food-allergic, individuals and their age-matched controls were included in this study. PBMCs were analyzed by flow cytometry ex vivo or were stimulated in vitro with peanut allergens, gliadin, or tetanus toxoid followed by analysis of proliferation and cytokine production in antigen-responsive cells. <b><i>Results:</i></b> We observed a significantly lower interleukin (IL) 17 production in CD4+ T cells of food-allergic individuals ex vivo (p < 0.02). In vitro, we found that IL-17 production in CD4+ T cells in response to all antigens tested was significantly impaired in food-allergic subjects compared to healthy controls (Ara: p < 0.005; gliadin: p < 0.004; TT: p < 0.03). No significant differences were observed between atopic and nonatopic individuals with no food allergy.<b><i> Conclusion:</i></b> Our results thus reveal a systemic, non-allergen-specific defect in Th17 responses to antigen stimulation in food allergic individuals, suggesting a role for Th17 cells in the control of food allergy and implicating IL-17 as a potential biomarker for tolerance to food antigens
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